Fluoride exposure to the developing fetal skeleton occurs from a number of sources, including maternal ingestion of fluoride tablets and fluoride containing drinking water. However, the effects of fluoride on the fetal skeleton are not well studied. In adult bone, the effects of exposure to high levels of fluoride include increased osteogenesis, altered osteoblast differentiation and function, increased bone mass and undemineralized osteoid. Although fluoride levels in maternal serum are low, the rapidly growing fetal skeleton may be similarly affected by the lower fluoride levels in the maternal serum. The objective of this proposal is to use the rat as an animal model to determine the alterations in bone development which may occur with prenatal fluoride exposure. The specific aims of this proposal are: (1) to further define the rat model by measuring the mineral and protein composition of bone from fetal rats prenatally exposed to fluoride as compared to controls; (2) to determine whether maternal fluoride exposure alters basic bone morphology and distribution of mineral in the fetal long bone. One day pregnant rats will be given drinking water containing either 0 or 100 ppm fluoride ad libitum. On gestational day 21, the rats will be killed, and maternal serum and fetal serum and bones will be collected. The fluoride content of these tissues will be determined. Amino acid analysis of bone protein will be done and used to compare total quantities of protein and collagen, and the amino acid profiles of bone from the control and experimental animals. Bone mineral contents will also be determined and compared. The effects of prenatal fluoride exposure on basic bone morphology and mineral distribution will be quantitated by computer analyzed image analysis. These pilot studies will define changes in fetal bone resulting from prenatal fluoride exposure, and allow future studies to determine the mechanisms by which fluoride may affect bone growth.